JAMA Surgery: Skin Infections Topic Collectionhttp://archsurg.jamanetwork.com/
en-usSun, 08 Jun 2014 00:00:00 GMTMon, 23 Jun 2014 21:50:04 GMTSilverchaireditor@archsurg.jamanetwork.comwebmaster@archsurg.jamanetwork.comTreatment for Necrotizing Soft-Tissue Infections More Skin in the Game http://archsurg.jamanetwork.com/article.aspx?articleID=1859985
Sun, 01 Jun 2014 00:00:00 GMTSawyer RG. <span class="paragraphSection">The article by Bulger et al represents an advance in the world of surgical infections as the first interventional trial using an immunomodulatory agent to treat necrotizing soft-tissue infections. Any prospective interventional study is difficult to execute, and one in such a complicated disease state with such severe morbid effects is even more laudable.</span>149653653610.1001/jamasurg.2013.4870http://archsurg.jamanetwork.com/article.aspx?articleID=1859985A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections A Randomized Clinical Trial http://archsurg.jamanetwork.com/article.aspx?articleID=1859986
Sun, 01 Jun 2014 00:00:00 GMTBulger EM, Maier RV, Sperry J, et al. <span class="paragraphSection"><div class="boxTitle">Importance</div>Necrotizing soft-tissue infections (NSTI) have high morbidity and mortality rates despite aggressive surgical debridement and antibiotic therapy. AB103 is a peptide mimetic of the T-lymphocyte receptor, CD28. We hypothesized that AB103 will limit inflammatory responses to bacterial toxins and decrease the incidence of organ failure.<div class="boxTitle">Objectives</div>To establish the safety of AB103 in patients with NSTI and evaluate the potential effects on clinically meaningful parameters related to the disease.<div class="boxTitle">Design, Setting, and Participants</div>A prospective, randomized, placebo-controlled, double-blinded study was performed in 6 academic medical centers in the United States. Participants included adults with NSTI. Of 345 patients screened, 43 were enrolled for the intent-to-treat analysis, and 40 met criteria for the modified intent-to-treat analysis; 15 patients each were included in the high-dose and low-dose treatment arms, and 10 in the placebo arm.<div class="boxTitle">Intervention</div>Single intravenous dose of AB103 (0.5 or 0.25 mg/kg) within 6 hours after diagnosis of NSTI.<div class="boxTitle">Main Outcomes and Measures</div>Change in the Sequential Organ Failure Assessment score within 28 days, intensive care unit–free and ventilator-free days, number and timing of debridements, plasma and tissue cytokine levels at 0 to 72 hours, and adverse events.<div class="boxTitle">Results</div>Baseline characteristics were comparable in the treatment groups. The Sequential Organ Failure Assessment score improved from baseline in both treatment groups compared with the placebo group at 14 days (change from baseline score, −2.8 in the high-dose, −2 in the low-dose, and +1.3 in the placebo groups; <span style="font-style:italic;">P</span> = .04). AB103-treated patients had a similar number of debridements (mean [SD], 2.2 [1.1] for the high-dose, 2.3 [1.2] for the low-dose, and 2.8 [2.1] for the placebo groups; <span style="font-style:italic;">P</span> = .56). There were no statistically significant differences in intensive care unit–free and ventilator-free days or in plasma and tissue cytokine levels. No drug-related adverse events were detected.<div class="boxTitle">Conclusions and Relevance</div>AB103 is a safe, promising new agent for modulation of inflammation after NSTI. Further study is warranted to establish efficacy.<div class="boxTitle">Trial Registration</div>clinicaltrials.gov Identifier: <a href="http://clinicaltrials.gov/show/NCT01417780">NCT01417780</a></span>149652853610.1001/jamasurg.2013.4841http://archsurg.jamanetwork.com/article.aspx?articleID=1859986